Nutritional programming of accelerated puberty in heifers: alterations in DNA methylation in the arcuate nucleus
Nutritional programming of accelerated puberty in heifers: alterations in DNA methylation in the arcuate nucleus
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DOI：
10.1095/biolreprod.116.144741
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Amstalden, Marcel
中科院分区：
文献类型：
--
作者：
Alves, Bruna R. C.;Cardoso, Rodolfo C.;Amstalden, Marcel
青少年时期的高体重增加率似乎在下丘脑内编程分子事件，导致青春期提前。DNA甲基化是一种控制基因表达的表观遗传机制，与代谢编程事件相关，并被认为在青春期过程中发挥作用。在这项研究中，在从幼年小母牛的弓状核（ARC）获得的基因组DNA中评估DNA甲基化，所述幼年小母牛从4.5至8.5月龄以低（0.5 kg/d;低增重，LG，n = 4）或高（1 kg/d;高增重，HG，n = 4）速率被喂食以增加体重（HG小母牛中预期的最早青春期在9月龄）。使用定制设计的寡核苷酸阵列针对印迹基因和与营养输入和青春期控制相关的基因，比较基因组杂交阵列用于识别LG和HG小母牛之间的差异甲基化区域。研究人员发现，与mRNA表达改变相关的基因组区域存在甲基化差异，这些基因的活性被报道参与了生长代谢（GHR）和青春期（HMGA 2）的调节。因此，在少年期增加的体重增加率改变了从ARC获得的基因组DNA的甲基化模式，这些变化可能参与了小母牛青春期年龄的编程。
High rates of body weight gain during the juvenile period appear to program molecular events within the hypothalamus, leading to advancement of puberty. Methylation of DNA, an epigenetic mechanism that controls gene expression, is associated with metabolic programming events and is proposed to play a role in the pubertal process. In this study, DNA methylation was assessed in genomic DNA obtained from the arcuate nucleus (ARC) of juvenile heifers fed to gain body weight at low (0.5 kg/d; low-gain, LG, n = 4) or high (1 kg/d; high-gain, HG, n = 4) rates from 4.5 to 8.5 mo of age (earliest puberty expected at 9 mo of age in HG heifers). Using a customdesigned oligonucleotide array targeted to imprinted genes and genes associated with nutritional inputs and the control of puberty, a comparative-genomic-hybridization array was used to identify differentially methylated regions between LG and HG heifers. Differential methylation of genomic regions associated with alteredmRNA expression was observed for genes whose activity has been reported to be involved in the modulation of growth and metabolism (GHR) and puberty (HMGA2). Hence, increased rates of body weight gain during the juvenile period alter the methylation pattern of genomic DNA obtained from the ARC and these changes may be involved in programming the age at puberty in heifers.Summary SentenceIncreased rates of body weight gain during the juvenile period alter the methylation pattern of genomic DNA obtained from the ARC and these changesmay be involved in programming the age at puberty in heifers.